BackgroundMultiple sclerosis (MS) is the most common cause of neurological disability in young adults worldwide and approximately half of those affected are in Europe. The assessment of differential incidence and prevalence across populations can reveal spatial, temporal and demographic patterns which are important for identifying genetic and environmental factors contributing to MS. However, study methodologies vary and the quality of the methods can influence the estimates. This study aimed to systematically review European studies of incidence and prevalence of MS and to provide a quantitative assessment of their methodological quality.MethodsA comprehensive literature search was performed to obtain all original population-based studies of MS incidence and prevalence in European populations conducted and published between January 1985 and January 2011. Only peer-reviewed full-text articles published in English or French were included. All abstracts were screened for eligibility and two trained reviewers abstracted the data and graded the quality of each study using a tool specifically designed for this study.ResultsThere were 123 studies that met the inclusion criteria. The study estimates were highly heterogeneous, even within regions or countries. Quality was generally higher in the more recent studies, which also tended to use current diagnostic criteria. Prevalence and incidence estimates tended to be higher in the more recent studies and were higher in the Nordic countries and in northern regions of the British Isles. With rare exceptions, prevalence and incidence estimates were higher in women with ratios as high as 3:1. Few studies examined ethnicity. Epidemiological data at the national level was uncommon and there were marked geographical disparities in available data, with large areas of Europe unrepresented and other regions well-represented in the literature. Only 37% of the studies provided standardized estimates.ConclusionsDespite the breadth of the literature on the epidemiology of MS in Europe, inter-study comparisons are hampered by the lack of standardization. Further research should focus on regions not yet studied and the evaluation of ethnic differences in MS prevalence and incidence. National-level studies using current diagnostic criteria, validated case definitions and similar age- and sex-standardization would allow better geographical comparisons.

Remyelination is the generation of new myelin sheaths after injury facilitated by processes of differentiating oligodendrocyte precursor cells (OPCs). Although this repair phenomenon occurs in lesions of multiple sclerosis patients, many lesions fail to completely remyelinate. A number of factors have been identified that contribute to remyelination failure, including the upregulated chondroitin sulfate proteoglycans (CSPGs) that comprise part of the astrogliotic scar. We show that in vitro, OPCs have dramatically reduced process outgrowth in the presence of CSPGs, and a medication library that includes a number of recently reported OPC differentiation drugs failed to rescue this inhibitory phenotype on CSPGs. We introduce a novel CSPG synthesis inhibitor to reduce CSPG content and find rescued process outgrowth from OPCs in vitro and accelerated remyelination following focal demyelination in mice. Preventing CSPG deposition into the lesion microenvironment may be a useful strategy to promote repair in multiple sclerosis and other neurological disorders.

BackgroundThe onset of secondary progression is a pivotal event in the course of relapsingeremitting (RR) multiple sclerosis (MS). Patients with secondary progressive MS (SPMS) experience continuous worsening of symptoms independent of the occurrence of relapses. Possible risk factors associated with the onset of SPMS remain under investigated in natural history studies of MS disease course. Methods We used KaplaneMeier survival analyses and Cox regression models to investigate the influence of gender, onset age and onset symptoms on time to and age at SPMS in British Columbia (BC) MS patients with a RR disease onset who were not exposed to immunomodulatory drugs. Results Of 5778 patients in the BCMS database with definite MS, 5207 (90%) had an RR onset. Median time to SPMS was 21.4 years (95% CI 20.6 to 22.2), reached at a median age of 53.7 years (95% CI 53.1 to 54.3). Male gender and motor onset symptoms were associated with a shorter time to and a younger age at SPMS. A younger age at disease onset was associated with a longer time to SPMS but also with a younger age at secondary progression. Other onset symptoms were not associated with time to, or age at, SPMS. Conclusions We identified three factors influencing the onset of SPMS in untreated patients with RRMS: motor onset symptoms and male gender were associated with both a shorter time to and a younger age at SPMS. A younger age at disease onset should not be viewed as indicating a better prognosis.

References for this review were identified from searches of Pubmed (from 1966 to 2005) and the Cochrane Library (2005, Issue 2) with the search terms